Cloning and characterization of muscle-specific kinase in chicken

Muscle-specific kinase (MuSK) is part of the receptor complex that is invol ved in the agrin-induced formation of the neuromuscular junction. In the ro dent, prominent mRNA expression of MuSK is restricted to skeletal muscle wh ile the expression of agrin can also be detected in brain and certain nonne uronal tissues. The recent identification of Xenopus MuSK reveals that MuSK can be detected in tissues other than skeletal muscle, such as the neural tube, eye vesicles, and spleen. In this study, we describe the cloning and characterization of the chicken ortholog of MuSK and demonstrate that the r egulation of MuSK expression in muscle is conserved from avian to rodent. A bundant mRNA expression of MuSK can be detected in early embryonic chick mu scle and is up-regulated after nerve injury. More importantly, we also demo nstrate that, in the chicken, MuSK mRNA is expressed during development in brain and liver, suggesting possible novel functions for MuSK. Furthermore, the regulatory profile of MuSK expression in chick muscle closely parallel s that observed for acetylcholine receptor, in terms of both mRNA expressio n and protein localization. Finally, studies with paralyzed chicken muscle as well as with cultured chick myotubes demonstrate the dependence of MuSK on both electrical activity and trophic factors.